AMINAS: ESTRUCTURA; PROPIEDADES Y SINTESIS

Las aminas son derivadas del amoniaco

H H N .. H

H N .. H R H

R N .. R R

R N .. R

amonaco amina 1ria.

amina 2ria

amina 3ria

AMIDAS: Derivadas de cidos carboxlicos AMINAS: Derivadas del amoniaco

Dopamine
cardiotnico

Epibatidin,
analgsico
N
2

H HO

NHCH3

HO OH
epi efri
estimul te

3CO

OC OC
3

renalina
rener ic

mezcalina
alucinogeno

Morphina
Narctico, analgsico

Propiedades fsicas de aminas alcoholes y alcanos

Compuesto P. de f . (C) -182.5 -93.5 -97.5 P de eb. (C) -161.7 -6.3 65.0 (CH3CH2)2NH CH3CH3 CH3CH2NH2 CH3CH2OH -183.3 -81.0 -114.1 -88.6 16.6 78.5 (CH3CH2CH2)2NH -40.0 (CH3CH2CH2)3N CH3CH2CH3 CH3CH2CH2NH CH3CH2CH2OH -187.7 -83.0 -126.2 -42.1 47.8 97.4 NH3 H2O -77.7 0.0 -33.4 100.0 -94.0 110.0 155.0 (CH3CH2)3N -48.0 -114.7 56.3 89.3 Compuesto P. de f . (C) -93.0 -117.2 P de eb. (C) 7.4 2.8

CH4 CH3NH2 CH3OH

(CH3)2NH (CH3)3N

Caractersticas espectroscpicas del gupo amina IR: Las aminas primarias y secundarias muestran una banda de absorcin debido al estiramiento N-H en la zona de 3250-3500 cm-1
1H

RMN: Los hidrgenos de las aminas suelen dar seales anchas. El desplazamiento qumico depende principalmente de la velocidad de intercambio de los protones con el agua presente en el solvente y del grado de formacin de puentes de hidrgeno

Propiedades Fsicas y Estructurales de las Aminas

En las aminas el nitrgeno tiene una hibridacin tipo sp3, formando un arreglo tetrahdrico aproximado

105.9 H H N 112.9 1.01 A

1.74 A CH3

El trmino piramidal es el usado frecuentemente para describir la geometria adoptada por el nitrgeno y los tres sustituyentes

1.01A

105.9

1.47A

112.9

piramidal

La geometria tetrahdrica alrededor del tomo de nitrogeno de una amina sugiere que esta podria ser quiral si los tres sustituyentes fueran distintos, sirviendo el par de electrones como cuarto sustituyente

Imagen e imagen especular de la Etilmetilamina

H N

CH2CH3

CH2CH3 N CH3

espejo

CH3

Imagen e imagen especular de la Nmetiletanamina (etilmetilamina)

H CH C N H CH
espejo

CH CH N H CH

Sin embargo las aminas no son opticamente activas. Porque??? Las aminas no son configuracionalmente estables en el nitrogeno, debido a una rpida isomerizacin por un proceso llamado inversion
**

3 3

.
2

La inversion del nitrgeno rpidamente interconvierte a los dos enantimeros. El compuesto no exhibe actividad optica Barrera energtica entre 5 y 7 kcal/mol

H3CH2C N H CH3
s

CH2CH3 N H CH3

CH3 CH2

N
H CH3

-N quiral

R H N R1

N R

R1

N M N

La existencia de enantimeros separables, para este compuesto, se debe a la imposibilidad de inversin del tomo de nitrgeno

Nombrando a las aminas

Segn Chemical Abstracts

CH3 CH3NH2 CH3CHCH2NH2

H2N

Metanamina 2-metil-1-propanamina (R)-trans-3-Pentenamina

NH2 H 2N H 2N NH2

1,4-Butanediamina (Putrescina)

1,5-Pentanediamina (Cadaverina)

Acidez y Basicidad de Aminas A semejanza con los alcoholes, las aminas pueden comportarse como cidos y como bases
Aminas actuan como cidos R H Ka +

:B

mi as act an como ases H R Kb

2

+ :A

Amines As Bases
Amines are employed commonly as bases in organic synthesis. Amine bases can operate in two ways: as Passive Bases whose synthetic role is simply to neutralise any acid that is generated as a by-product in a reaction; or as Active Bases whose role is to remove protons from substrates in order to facilitate a reaction.
Base Pyridine Ammonia Trimethylamine Triethylamine Hydroxide Methoxide t -Butoxide Anilina Basicity (~pKa) 5.2 9.2 9.8 11.0 15.7 16.0 18.0 4.63

Cuanto mayor es el pKa, menor es la acidez y mayor la basicidad.

Los iones amonium son debilmente cidos

H + H2 Ka + + H2 H

+ H2

H2
+ H

RNH2 Ka=

H2

H + H2

K a = 10-10 p K a = 10

NH4+ CH3NH3+ (CH3)2NH2+ (CH3)3NH+ pKa 9.24 10.62 10.73 9.79

Loss of conjugation of the nitrogen lone pair with the phenyl ring occurs if the amine nitrogen becomes protonated. Consequently, aniline is less basic. Enhanced s-character for the sp2 hybridised nitrogen render it more electronegative in comparison to a normal sp3 nitrogen and therefore decreasing its ability to become positively charged.

The passive bases (in general the weaker bases) are employed in reactions that require a base in order to attain completion. An example of this is the acylation of primary or secondary amines. In these reactions, bulky, nonnucleophilic bases such as Hnigs base (diisopropylethylamine) are frequently used. More powerful amine bases are required when the reaction involves removal of a proton from a substrate in order to generate an anionic intermediate. The most commonly employed strong organonitrogen base is lithium diisopropylamide (LDA) (a metal amide) this is produced by treating diisopropylamine with butyl lithium. Reactions using LDA are typically carried out at 78 C in order to avoid detrimental side reactions. In the case of substrates where two acidic protons can be abstracted by base, treatment with LDA leads to the kinetic (i.e. sterically least hindered) product. LDA is not as strong a base as BuLi, however, it is too hindered to act as a nucleophile. In the uncommon case where it does participate as a nucleophile, LDA can be replaced by the even bulkier base, lithium hexamethyldisilazide. Strong bases such as LDA are not always required to abstract protons from substrates. In the case of elimination reactions, milder organonitrogen bases such as 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4diazabicyclo[2.2.2]octane (DABCO) or even pyridine are employed.

DBN

DBU

DABCO

It is clear that electron-donating groups stabilise the positive charge of the ammonium nitrogen and therefore enable the above equilibrium to lie further to the right hand side. Consequently, the association constant is reduced and the pKa is subsequently raised. This is clearly evident by consideration of ethylamine and diethylamine (note that steric effects actually serve to decrease the basicity of the nitrogen in triethylamine). The basicity of the nitrogen atoms in amines such as aniline and pyridine are dramatically affected by aromaticity and the ability to form numerous canonical forms via resonance of the amines lone pair of electrons with the benzene p-system.

Basicidad de las aminas Aminas deprotonan al agua, en baja proporcin y generan iones amonio e hidroxilos
H

RNH2 + HOH amina

Kb

+ : RNH2 + H O ion amoni m

H + RNH2

: HO = 10-4

Kb =

RNH2

K b = 10-4

Las aminas son cidos muy dbiles, mas dbiles que los alcoholes La deprotonacin de aminas requiere de bases extremadamente fuertes, tales como los alquillitios Preparacin del LDA

CH3CH2CH2CH2Li N H N-(1-metiletil)-2-propanamina (diisopropilamina) - CH3CH2CH2CH2H

Li+ N

Litio diisopropilamida, LDA

Separacin de compuestos orgnicos cidos, bsicos y neutros en medio acuoso

O RCOH + RNH2 + RX
extraccin con NaHCO 3

ase acuosa
O

ase orgnica

RNH2 + RX
extraccin con HCl
O- Na+ acidi icacin con HCl

ase acuosa RNH3+ClNaOH aq

ase orgnica

RX

RNH2
R OH

Amines are unusually versatile species very few other systems possess the ability to act as both a base and a nucleophile so readily. The nucleophilic character of an amine can usually be easily quenched by addition of acid to the amine protonation of the nitrogen by dative attack by the lone pair of the nitrogen render it unable to attack electrophilic carbon sites.

pKb de una serie de aminas simples NH3 CH3NH2 (CH3)2NH (CH3)3N pKb 4.76 3.38 3.27 4.21

pKb NH3 > CH3NH2 > (CH3)3N > (CH3)2NH

NH2
Bencenamina (anilina) pKb 9.37
: NH2

Ciclohexanamina pKb 3.34

Sntesis de aminas
Por alquilacin Alquilacin del amoniaco
Primera alquilacin

H3N + CH3Br (CH3NH3)+Br- + NH3

Alquilaciones siguientes

(CH3NH3)+Brbromuro de metilamonium

CH3NH2 + HNH3+BrMetanamina (metilamina)

CH3NH2

CH3Br

(CH3)2NH

CH3Br

(CH3)3N

CH3Br

(CH3)4N+Br-

La mezcla de productos limita el uso de la alquilacin directa

Sintesis de Gabriel de aminas primarias

O O OH OH NH3 300 -H2O H H2 O 97% O 97% K2 O 3 O R H2 r DMF, 100 N K+ -K r O

O ci o ftlico

O H2SO4 H 2O 120C + H3 NCH2R +

O OH OH 97% O NaOH H2 O

NCH 2R

O 93%

O O-Na+ H2NCH2 R + O-Na+ O

Por reduccin
Desaplazamiento por cianuro y reduccin
RX + -CN RCN + X-

RCN LiAlH4 o H2 cat. RCH2NH2 Se obtiene una amina con un carbono ms que el halogenuro de partida

Ej.: Br(CH2)8Br + NaCN

1,8-dibromooctano

NC(CH2)8CN
decanodinitrilo

H2N(CH2)10NH2
1,10-decanodiamina

Desplazamiento por azida y reduccin

Br

Na+N3-

/EtOH

+ N N N-

1. LiAlH4 (Et)2O 2. H+, H2O

NH2

(SN2) ciclopentilpropilazida 91% 3-ciclopropilpropanamina 89%

Amines via Reduction Reactions There is a wide range of organonitrogen substrates that can be readily reduced to the corresponding amine. The table below indicates the type of substrates that can be reduced and what reducing agent will facilitate the reduction.
Group Imine Amide Nitro Nitrile Reducing Reagents LiAlH4, NaBH4, H2/cat LiAlH4 LiAlH4, H2/cat, Sn/HCl, NaSH LiAlH4, H2/Raney Ni

Reactions with Aldehydes and Ketones

Primary and secondary amines react with aldehydes and ketones via nucleophilic attack at the electrophilic carbonyl carbon centre (the reaction is often catalysed by acid). In the case of primary amines, imines are produced whereas as in the case of seconday amines the products are enamines (the by-product in both reactions is water).

Sintesis de aminas por aminacin reductiva



Esta sintesis comienza con la condensacin de aminas con compuestos carbonilicos para producir iminas, las que son reducidas por hidrogenacin cataltica o hidruros

condensacin

reduccin

Sntesis de aminas a partir de amidas

a) Por reduccin con hidruros O + H2NR amina ra ) Por reordenamiento de Hofman
R H 2N amida r2, NaOH, H2 O amina con un car ono menos ue la amida de partida RNH2 CO2

ase -HCl amida O

LiAlH4 ( H3CH2)2O

RCH2NHR amina 2da